The Israeli military, which has long accused Palestinian militants of using schools and other civilian infrastructure, confirmed the strike "in the area of the school" in Gaza City.
It said in a statement the school complex was used as a militant hideout and housed "a Hamas weapons manufacturing facility".
The civil defence agency said Ihab al-Ghusain, the Hamas government's deputy labour minister, was among those killed in the strike on the Holy Family school.
The strike came a day after a UN-run school in the central Nuseirat refugee camp was hit, in an attack that the Gaza health ministry said killed 16 people and drew condemnation from the United Nations. Israel said militants were hiding there.
Hamas has repeatedly denied Israeli accusations that militants were hiding in civilian infrastructure.
The vast majority of the Gaza Strip's 2.4 million people have been displaced by the war, now in its 10th month, and many have taken shelter in UN-run schools across the besieged territory.
The UN agency for Palestinian refugees, UNRWA, expressed outrage at the repeated attacks on its premises.
"Another day. Another month. Another school hit," UNRWA chief Philippe Lazzarini said on social media platform X.
UNRWA spokesperson Juliette Touma told AFP that 190 -- or more than half -- of the agency's facilities in Gaza have been hit, "some more than once", since the war began with Hamas's October 7 attack on Israel.
"When the war started we closed the schools and they became shelters," she said.
Up to Thursday, 194 UNRWA workers had been killed, Touma added.
Since then, the UN agency reported separately that another two were killed in an Israeli attack on Saturday.
There have been 450 "incidents" involving UNRWA buildings during the war, Touma said, saying the damage is "unprecedented in the history of the UN".
"Any hits on UN facilities are shocking and there has been a blatant disregard for international humanitarian law in regard to this conflict," she added.
The October 7 attack on southern Israel resulted in the deaths of 1,195 people, mostly civilians, according to an AFP tally based on Israeli figures.
Hamas militants also seized hostages, 116 of whom remain in Gaza including 42 the military says are dead.
In response, Israel has carried out a military offensive that has killed at least 38,153 people in Gaza, also mostly civilians, according to data from the territory's health ministry.
